Research Repository

See what's under the surface

Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action

Stocks, Michael; Alcaraz, Lilian; Bailey, Andrew; Bonnert, Roger; Cadogan, Elaine; Christie, Jadeen; Dixon, John; Connolly, Stephen; Cook, Anthony; Fisher, Adrian; Flaherty, Alice; Humphries, Alexander; Ingall, Anthony; Jordan, Stephen; Lawson, Mandy; Mullen, Alex; Nicholls, David; Paine, Stuart; Pairaudeau, Garry; Young, Alan

Authors

Michael Stocks michael.stocks@nottingham.ac.uk

Lilian Alcaraz

Andrew Bailey

Roger Bonnert

Elaine Cadogan

Jadeen Christie

John Dixon

Stephen Connolly

Anthony Cook

Adrian Fisher

Alice Flaherty

Alexander Humphries

Anthony Ingall

Stephen Jordan

Mandy Lawson

Alex Mullen

David Nicholls

Stuart Paine

Garry Pairaudeau

Alan Young

Abstract

A series of dibasic des-hydroxy β2 receptor agonists has been prepared and evaluated for potential as inhaled ultra-long acting bronchodilators. Determination of activities at the human β-adrenoreceptors demonstrated a series of highly potent and selective β2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by; onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i. t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultra-long acting inhaled β2 receptor agonist with rapid onset of action.

Journal Article Type Article
Publication Date Apr 10, 2014
Journal ACS Medicinal Chemistry Letters
Print ISSN 1948-5875
Electronic ISSN 1948-5875
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 5
Issue 4
Pages 416-421
Institution Citation Stocks, M., Alcaraz, L., Bailey, A., Bonnert, R., Cadogan, E., Christie, J., …Young, A. (2014). Discovery of AZD3199, An Inhaled Ultralong Acting β2 Receptor Agonist with Rapid Onset of Action. ACS Medicinal Chemistry Letters, 5(4), 416-421. https://doi.org/10.1021/ml4005232
DOI https://doi.org/10.1021/ml4005232
Publisher URL https://pubs.acs.org/doi/10.1021/ml4005232
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
Additional Information This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for
publication in ACS Medicinal Chemistry Letters copyright © American Chemical Society after peer review. To access the final edited and published work see: http://pubs.acs.org/doi/ipdf/10.1021/ml4005232

Files

Mstocks_ACS__Final_draft_copy.pdf (384 Kb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf




Downloadable Citations